Symptomatic uterine fibroids cause severe and chronic pain and discomfort for thousands of childbearing-age women. While magnetic resonance-guided focused ultrasound (MRgFUS) has been demonstrated as a safe and non-invasive therapy for fibroids during the last decade, the treatment response of some fibroids to MRgFUS is poor. Specifically, fibroids with high T2-weighted signal intensity (T2wSI) on pretreatment MR imaging are difficult to treat successfully and blood flow is hypothesized to play a major role in the outcome of MRgFUS fibroid treatments. However, there is a lack of research investigating the cause of poor response in high T2wSI fibroids and the potentially related effects of blood flow on treatment outcomes. This proposal addresses each of these problems in two specific aims. The proposed research will involve a pre-surgical MR imaging session in women undergoing hysterectomy for fibroid-related symptoms. Because many of the prescribed measurements cannot be obtained in the clinical setting, the remainder of the study will be performed following surgery in a unique ex vivo perfused uterine fibroid model designed to maintain tissue viability and mimic the in vivo fibroid environment. The first aim seeks to 1) characterize the acoustic and thermal properties of uterine fibroids, 2) identify the distribution and magnitude of blood flow with extracellular and blood pool MR contrast agents, and 3) link those properties to the in vivo and ex vivo MR characteristics of T2-weighted signal intensity and heterogeneity. The second aim includes 1) implementing a noncontrast MR perfusion sequence for in vivo and ex vivo imaging of uterine fibroids, 2) performing volumetric MRgFUS ablation of ex vivo fibroid tissues, and 3) correlating blood flow measurements with treatment outcomes of thermal dose, non-perfused volume, and histological tissue necrosis. By optimizing MR measurements in the ex vivo setting with later implementation in vivo, this study will develop MR protocols that can be immediately and effectively applied in the clinic. The long-term benefits of this work include the potential for improved treatment outcomes and patient selection guidelines for MRgFUS treatments of symptomatic uterine fibroids.